Lecture 10 Flashcards
What are the myths surrounding mental illness ?
- People with mental illness are violent and dangerous
- People with metal illness are poor or less intelligent
- Mental illness is caused by a personal weakeness
- Mental illnes is a single, rare disorder
How is mental illness complicated ?
- Comorbidities are common
- Many people who fit a diagnosis for one mental disorder may partially fit the diagnosis for another as well
- People may not completely match any specific diagnosis
What is schizophrenia ?
a split between the emotional and intellectual aspects of experience
What was schizophrenia previously called ?
Dementia Praecoz (“premature dementia”)
What are the positive symptoms of schizophrenia ?
- Disorganized speech
- Disorganized behaviour
- Hallucination
- Delusions
What are the negative symptoms of schizophrenia ?
- Flattened affect and or anhedonia
- Speech minimized
- Lack of motivation
- Social withdrawl
What are the cognitive symptoms of schizophrenia ?
- Poor sustained attention
- Low psychomotor speed/catatonia
- Poor learning and memory
- Poor abstract thinking/problem solving
What symptoms fall under complex syndrome ?
- Psychosis
- Emotional/Affective symptoms
- Motivtional impairment
- Cognitive impairment
What are the types of schizophrenia ?
- Paranoid
- Catatonic
- Disorganized
- Residual
- Undifferientiated
What is paranoid schizophrenia ?
Frequent visual and auditory hallucinations/delusions, disprganized speech, trouble concentrating, and significant behavioural impairment
What is catatonic schizophrenia ?
Excessive movement (catatonic excitement), or decreased movement (catatonic stupor)
* inability to speak (mutism). mimicking owrds (echolalia) and mimicking actions (echopraxia)
* Rarest
What is disorganized schizophrenia ?
Disorganized behaviours and nonsencial speeach in the absence of delusions and hallucinations
* Most common
What is residual schizophrenia?
Previously diagnosed - no longer experiencing prominent symptoms
* still exhibited symtoms including a flattened affect, psychomotor difficulties, and disturbed speech
What is undifferentiated schizpphrenia ?
Symptoms fit into more than one subtype of schizophrenia
What is the prevalence of schizophrenia ?
- Prevelance higher in men than women (7:5 ratio)
- More prevenlent in prosperous countries than 3rd world
How is genetics tied to schizophrenia ?
- People with closer genetic relationships have higher concordance for schizophrenia
- Adopted children studies suggest a genetic role (Prenatal environment of the biological mother cannot be discontinued)
- Environmental influence, such as family environment, shown to have a role
- No common genetic variant produces more than small increase in the probability of schizophrenia
- A few rare genes are known to greatly increase the risk of schizophrenia, mostly by disrupting the development of glutamate synapses or by interfering with the immune system
What does DISC1 control ?
Disrupted in schizophernia 1 controls differentiation and migration of neurons in brain development
What is the DISC1 protein important for ?
The DSC1 protein is important for neurodevelopment
What has human studies shown regarding gene mutations ?
- High prevalence of “broken copy” in Large Scottish family over 5 generations - development of schizophrenia, bipolar & other mood disorders
- Meta-analysis confirmed overall association and found strongest estimate in Chinese population
What has animal studies shown on gene mutations ?
Mutant mice with no DISC1 in brain stem stem cells show behaviours that mimic schizophrenia
What is NRG1 important for ?
Neuregulin 1 protein is important for neurodevelopment
What do association studies show regarding gene mutations ?
- Iceland population - NRG1 risk allele doubles the risk of schizophrenia
- Extended to Scottish, Swedish and Chinese populations
What is NRG1 associated with ?
Associated with bipolar disorder and creativity, independent of schizotypal traits
What is the recent popular hypothesis ?
Not just one gene, but new mutations in any one of hundreds of genes
What was found regarding microdeletions and microduplications ?
- Found in 15% schizophrenia patients; 20% if onset before 18 years. Compared to 5% in control group
- Not random, but selective for genes that are important for production of proteins involved in neurodevelopment and nognitive function
What is the neurodevelopmental hypothesis ?
Suggests abnormailities in the neonatal development of the nervous system leads to mild abnormalities of brain anatomy and major abnormalities in behaviour
* abnormalities could result from genetics or other influences
* Environmental influences later in life aggravate the symptoms
What is the season-of-birth-effect ?
Babies born in late winter and early spring motnhs are at higher risk of “positive” schizophrenia
What are some viral infections that a mother can get ?
- Increase cytokines in the mother that impair brain development of fetus
- Cause fever that damages the fetal brain
What is the research evidence found on viral infections and schizphrenia ?
- Babies born from mother who contracted flu in 1st trimester 7x more likely to develop schizophrenia
- Increased schizophrenia rates among people born 2-3 months after major influenza epidemics
What are the risk factors falling under the neurodevelopmental hypothesis ?
- Poor nutrition of the mother during pregnancy
- Premature birth
- Low birth weight
- Complications during delivery
- Extreme stress of mother during pregnancy
- Immunological rejection
- Other infections during pregnancy
- Postnatal stressors
What is the two-hit hypothesis ?
Schizophrenia is the result of a combination of a genetic predisposition and impacts from the environement in prenatal/neonatal development, later in life, or both
What are the brain abnormalities tied to schizophrenia ?
- Enlarged lateral ventricle and prominent sulci
- Decreased tissue cerebral gray matter
- Smaller PFC and hippocampus
- Less gray matter and white matter
- Reduced cortical connectivity and activity
- Glial reductions (glial theory): oligodentrocytes and mylein integrity (DISC1); altererd microglia in temporal and frontal lobes; astrocyte glutamate transporters in PFC
What is the dopamine hypothesis ?
Positive symptoms are caused by over-activity of synapses between DA neurons of then VTA and nucleus accumbems and aymygdala (Mesolimbic)
What do antipsychotic drugs (chlorpromazine) do ?
Antipsychotic drugs block DA receptors
* Block D2 receptors, preventing receptor activation (antagonist)
What resembles shizophrenia ?
Amephetamine psychosis resembles schizophrenia
* amphetamines (and cocaine) block DA reuptake thus increase DA levels (agonist)
* Amphetamines exacerbate symptoms
What is the glutamate hypothesis ?
Schizpohrenia due to excessive glutamate
Whay occurs regarding the glutamate hypothesis ?
- Mesolimbic pathway overactivated
- Glutamate neurons fail excite GABA neurons (GABA=Inhibitory)
- Glutamate neurons fail to excite DA neurons (negative symptoms)
What blocks NMDA receptors ?
PCP (angel dust) and ketamine (date rape drug) block N-methyl-D-asparate receptors
* they create all symptoms
* this effect is not observed in preadolesence
How were schizophrenic patients treated before the mid 1950’s ?
Most people with schizophrenia were idenfinitely confined to mental hospitals
How are schizophreniz patients treated today ?
Effective drugs and outpatient treatment
What does Glycine or D-serine do ?
Stimulate NMDA receptors and reduce schizophrenic symptoms
* effective in reducing negative symptoms
What does Clozapine do ?
Atypical antipsychotic -Clozapine- increases release of DA in PFC and decreases DA in nucleus accumbens - addresses all symptoms
What is a partial agonist ?
Serves as an agonist in regions of low concentration of the normal ligand and as an antagonist in regions of high concentrations
What disorders are included in Major Affective Disorders ?
Includes Major Depressive Disorder (MDD) and Bipolar Disorder
What is MDD ?
- Unipolar
- Unremetting depression
What is Bipolar Disorder ?
Cyclical periods of mania and depression
* BP1: full-blown mania
* BP2: hypomania
* Cyclothymic
What are the symptoms of MDD ?
- Hopelessness and helplessness
- Worthlessness. self-hate, guilt
- Agitation/irritability
- Weight loss
- Concentration
- Fatigue/lack of energy
- Isolation/withdrawl
- Anhedonia
- Sleep
- Suicidal thoughts
What is the concordance b/w MZ and DZ twins regarding MDD ?
Concordance in MZ twin is ~65% vs 13% in DZ twins
What is the monoamine hypothesis ?
Depression is caused by low level of activity of one or more monoaminergic synapses
* Dpamine (DA) - anhedonia
* Nonrepinephrine (NE) - (psychomotor symptoms)
* Serotonin (5HT) - (rumination, impulsive thoughts)
What is the evidence for the monoamine hypothesis ?
Introduction of monoamine oxidase (mao) inhibitors
* Block degradation of monoamines
What is the neurology of MDD ?
Decreased activity in left and increased activity in right PFC
Amygdala
* 50-70% increased blood flow and metabolism in amygdala
* activity correlated with severity of symptoms
* faulty amygdala - PFC coupling
What is ACC ?
Attentional processes that regulate cognition and emotion
What is the role of neurogenesis in MDD ?
- Hypothesis: Stress exposure decreases neurogenesis in the dentate gyrus of the hippocampus which causes depression
- Evidence: Treatment with anti0depressant meds alleviate symtpoms at the same time that they facilitate neurogenesis in the rodent HC
- Evidence: Exercise enhances neurogenesis in the HC of both animals and humans and alleviates deprresive symptoms
What do antidepressant drugs do ?
- SSRI and NRIs - enhance 5-HT and NE (respectively) by inhibiting reuptake of the neurotransmitter
- Tricyclics (TCAS) - Block tranporter proteins that reabsorb serotonin, dopamine, and norepinephrine into the presynaptic neuron after release
- MAOIs - enhance monoamines by inhibiting MAO
What is Trancranial Magnetic Stimulation ?
Pulses of magnetic energy focused over a particular surface along the scalp to deactivate neurons
What is Electroconvulsive Therapy (ECT) ?
An electrically induced seizure used for treatment of severe depression
* Non-responders or suicidal patients
* Applied every other day for a period of two weeks
* Side effects include memory loss - can be minimized if shock is localized to the right hemisphere
What are the simplest and least expensive treatments for MDD ?
- Moderate-intensity exercise
- Alter the sleep scheduele
Periodic sleep deprevation sometimes helpful
* Seasonal affective disorder (SAD)
What are the symptoms of bipolar disorder ?
Depressive symptoms
Manic episodes
* Elevated moof: hyperactive, increased energy, high self-esteem (false), grandoise/delusions
* Racing thoughts
* loud-rapid speech
* Reckless behaviour: binging, poor judgement, promiscuity, spending sprees
* Agitated or irritated
What is the concordance among MZ twins for Bipolar Disorder ?
Concordance in MZ twins is 80%
What is used to treat Bipolar Disorder ?
Lithium
* Stabilizes mood and prevents relaspe in mania or depression
* Exact mechanism is unknown, but shows neurotropic effects
* Works by decreasing glutamate activity and inflammation in the brain
What is anxiety ?
Unfoundded, unrealistic, chronic fear
What are the common types of anxiety disorders ?
- Generalized anxiety disorder
- panic disorder
- specific phobias
- OCD
- PTSD
What is GAD ?
Excessive uncontrollable anxiety and worry
* Common co-morbity with depression
* Women > Men
What are the symptoms of GAD ?
- Fatigue
- muscle tension
- restlessness
- irritability
- sleep distrubances
- concentration problems
What is Panic Disorder ?
Characterized by repeated and unpexcted panic attacks along with worry about future attacks
What are the symptoms of a panic attack ?
- chest pains
- rapid heartbeat
- shortness of breath
What is a phobia ?
An unreasonable or excessive fear of an object, situation, or activity
What are the three categories of phobia’s ?
- Agoraphobia
- Social phobia
- Specific phobias
What is agoraphobia ?
Fearful of a public place or being outside of the home to the extent that panic attack or extreme embarassment is possible
What is social phobia ?
A fear of social activity, especially of being scruntinized and embarassed
What are specfic phobias “?
Exaggerated fear of specific object/situations not covered by the other two
What are the risk factors of anxiety ?
Genetics
* heratibility of 31.6%
* 2x more likely to develop GAD if parents has a diagnosis
* Candidate geens that code for the monoaminergic system
Personality trait neuroticism, high stress sensitivity
Childhood maltreatment
Chronic or Traumatic Stress
How does anxiety look like in the brain ?
- Increased activation of amygdala and decreased activation of PFC while looking at angry faces
- In helathy controls, vmPFC decreases activation of amygdala, but not in persons with anxiety
- High levels of anxiety correlates with increased activation of amygdala, insular cortex and anterior cingulate cortex
What are obsessions ?
Thoughts, images, or impulses that are intrusice enough to cause marked rise in anxiety
What are compulsions ?
Ritualistic behaviours or mental acts that are designed to lower anxiety
When do obsessions and compulsions begin ?
Usually begins at ages 6-15 for females and 20-29 for males
How does OCD look like in the brain ?
Hyperactivity in
* Caudate nucleus (Basal Gnaglia): compulsivity and impulsivity
* Orbitofrontal cortex (OFC): obsessive thoughts
* Anterios cingulate cortex (ACC): emotion regulation
Dysregulation of cortico-basal ganglia-thalamo-cortical (CBGTC) loop
* System of neural circuits
Dysfuntion in 5HT and DA systems
What is PTSD ?
Occurs in some people after terrifying expeinces
What are some symptoms of PTSD ?
- Frequent distressing recollections
- Nightmares
- Avoidance of reminders of the event
- Exaggerated arousal in response to noises and other stimulu
How does PTSD look like in the brain ?
- The amygdala is esstential for the extreme emotional impact that produces PTSD
- Dysregulation of HPA-axis: Lower than normal cortisol levels and blunted cortisol response to acute stressor
- Smaller than average hippocampus
How is mental health tied to intelligence ?
Higher rates of mental illness in individuals with
* High IQ
* Artists
* Scientists
* “Geniuses”
